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39 Cards in this Set
- Front
- Back
Most Growth Factor action on normal cells is
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paracrine
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Cancer cells make their own _______
OR they... |
-growth factors
-or they tell the stroma to make them some |
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Cancer cells over-express _____ _____ _____
OR they... |
-growth factor receptors
-or they always have mutated receptors that are "always on" sending signals continuously even without growth factor |
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What do you see when there's an
Overexpression of EGF |
-80% squamous cell carcinomas of lung
-50% glioblastomas -80-100% epithelial tumors of head/neck |
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What do we see when there's an
Overexpression of ERBB2 |
25-30% of breast cancers
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In Signal Tranducing Proteins:
Inside the cell, mutations occur... |
further downstream, on the signally proteins
(inside the cell) |
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In Signaling Tranducing Proteins:
There is a direct signal to _______ without... |
-nucleus
-without growth receptor signal |
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In Signaling Tranducing Proteins:
Two most common mutations are in ______ and ______ |
-RAS
-ABL |
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In Signaling Transducing Proteins:
RAS - |
-most commonly mutated gene in human tumors
-small protein that binds GTP, GDP |
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In Signaling Transducing Proteins:
ABL - |
-tyrosine kinase
-translocation in chronic myelogenous leukemia from chromosome 9 to 22 -fuses with BCR there and make fusion protein that has constitutive activity |
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In Nuclear Transcription Factors:
Transcription Factors - |
regulate expression of proteins by controlling transcription of DNA
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Cancer-related mutations in transcription factors can result
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result in expression of more growth promoting genes like growth factor genes
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In Nuclear Transcription Factors:
MYC - |
-activates or repress:
-activates genes that encourage progression thru cell cycle like cyclins -repress genes that stops it |
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In Nuclear Transcription Factors:
MYC encourages ____ _____ and ____ _____ |
-aerobic glycolysis
-glutamine utilization |
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In Nuclear Transcription Factors:
MYC is an example of |
Burkitt's lymphoma
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Cyclins
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regulate progression through the cell cycle
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Cyclin-Dependent Kinases:
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-maintain orderly progression
-activated by binding to cyclins |
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Cyclin-Dependent Kinase Inhibitors:
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broad and selective inhibitors of CDKs
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All cancers seem to have mutations that disable
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the G1-S checkpoint
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All cancers seem to have ↑ _____ ___ and ____ ____
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-cyclin D
-CDK4 expression |
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All cancers, what is disabled by mutation or silenced?
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CDKIs
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Self-sufficiency of proliferation is opposed by 2 cellular pathways:
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-Apoptosis
-Senescence |
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How many hallmarks is there?
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6
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In Insensitivity to Growth Inhibition Signals:
Tumor suppressor genes "brakes" for |
proliferation
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In Insensitivity to Growth Inhibition Signals:
4 major targets: |
-RB (governor)
-TP53 (guardian) -TGF-Beta Pathway -Contact Inhibition pathways |
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In Insensitivity to Growth Inhibition Signals:
List characteristics of RB (6) |
-DNA-binding
-regulates G1-S checkpoint -is cell cycle clock (important in development) -common mutation -many viruses that are oncogenic bind RB -this gene involve in retinoblastoma (rare childhood cancer) |
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In Insensitivity to Growth Inhibition Signals:
List characteristics of TP53 (5) |
-Anoxia (absense of oxygen), DNA damage,
inappropriate signaling -encourage transcription of CDKI which stops cell cycle -Blocks G1 to S during repair -if no repair → induces senescence/apoptosis -Viruses can subvert (overthrow it) like RB |
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In Insensitivity to Growth Inhibition Signals:
TGF-Beta Pathway has normal proliferation inhibitor in which cells (3) |
-epithelial
-endothelial -hematopoetic |
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In Insensitivity to Growth Inhibition Signals:
TGF-Beta Pathways has mutations in - _____% of ______ ______ _____% of ______ ______ |
-100% of pancreatic cancers
-83% of colon cancers |
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In Insensitivity to Growth Inhibition Signals:
Transformed cells in Contact Inhibition does what? |
They don't show contact inhibition in cell culture
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In Insensitivity to Growth Inhibition Signals:
Contact Inhibition, _______ mediate cell-cell contact |
Cadherins
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In Insensitivity to Growth Inhibition Signals:
What faciliates E cadherin contact inhibition? |
NF2 gene product merlin
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In Insensitivity to Growth Inhibition Signals:
_____ gene product loss can be involved in loss of contact inhibition by... |
-APC (patients lots of polyps)
-destroying beta-catenin which can be a growth promoting transcription factor |
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APC -
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condition where patients get lots of polyps
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In Apoptosis:
-2 pathways are ______ & _____ -Both results in activation of _____ _______ |
-intrinsic (mitochondrial pathway), extrinsic
-caspase cascade |
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In Apoptosis:
The intrinsic or Mitochondrial Pathway, what happens? |
-cell injured (DNA damage, proteins misfolding)
-sensors in BCL-2 family activate Bax and Bak = make holes in mito's membrane -mito proteins like cytochrome c escape and activate caspase cascade |
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In Apoptosis evasion:
BAX-BAK pro-apoptotic action is regulated by |
BCL2 which is anti-apoptotic
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In Apoptosis evasion:
Mutations that activate BCL2 are common in |
B cell lymphomas
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How do cancer cells avoid autopagy?
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by mutation or taking over it to get "parts" to grow
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